PB2221: A SYSTEMATIC LITERATURE REVIEW DESCRIBING PROTECTIVE EFFECTS OF HBF IN SICKLE CELL DISEASE OUTCOMES
Authors: O. Mitelman, J. Barry, J. Bernhard, P. Bruno, C. Morabito, S. Snedecor, S. Ronnebaum
Journal: HemaSphere (2022)

Background: Patients with sickle cell disease (SCD) are vulnerable to a variety of clinical complications, including pain crises, acute chest syndrome (ACS), splenic sequestration, leg ulcers, stroke, and mortality. HbF (fetal hemoglobin) reduces disease severity and decreases the risk of SCD complications, but the degree of HbF’s protective effects has not been systematically explored. Aims: To characterize the clinical benefit of elevated HbF levels on patients with SCD. Methods: A systematic literature review (SLR) was performed in Embase, MEDLINE, and the Cochrane Library to identify all evidence describing HbF levels and/or longitudinal changes versus adverse outcome occurrence among patients with SCD in observational or interventional studies. Citations were screened and extracted by dual independent review. Weighted linear regression was performed to identify data trends where applicable. Variability in factors such as study design, outcomes analyses, and reporting methods may have contributed to the heterogeneity of results. Results: The SLR identified 2997 citations, from which 148 studies were selected for investigation. Within the 148 studies, 901 distinct analyses detailed the impact of HbF levels on SCD patient outcomes. Given the differences in study design, 4 different approaches were described in evaluating the impact of HbF levels: 1.) Average adverse outcome rates based on study-level HbF averages were investigated in 735 analyses. Weighted linear regression demonstrated a directional trend and supported HbF’s protective impact on outcomes such as among hospital admissions, ED visits, and hospital days. 2. The associations between patient-level HbF and adverse outcome occurrence were detailed in 109 analyses (see image). Higher HbF levels led to lower risk of adverse outcome occurrence (i.e., were protective) in 91 analyses (36 analyses were statistically significant and 55 were not significant or significance was not reported). 3. The average adverse outcome occurrence among patients segmented by HbF ranges/thresholds were described in 40 analyses. There was a lower rate of adverse outcomes in patients in the highest HbF range compared to patients in the lowest HbF range in 30 out of the 40 comparisons (10 were statistically significant, 13 were not significant, and 7 were not reported). 4. Study-level comparisons of average HbF levels of patients that experienced an adverse outcome vs. those that did not were described in 17 analyses. In 14 comparisons, patients not experiencing the outcome showed higher average HbF (9 were statistically significant, 5 were not significant), with the difference between the 2 groups ranging from 1.0%-7.1% of total Hb. Summary/Conclusion: The vast majority of studies demonstrated that elevated HbF values have a clinically meaningful benefit on SCD patient outcomes. Relatively small changes in HbF appear to protect patients against relevant adverse clinical outcomes.